The goal of this project is the development of a new, ultra-sensitive analytical tool for biomedical research that couples the precision separation capabilities of liquid chromatography (LC) with the detection sensitivity of accelerator mass spectrometry (AMS). This new technique, known as LC-AMS, will promote the study of biological molecules labeled with carbon-14 or tritium. AMS is a powerful tool for the detection of 14C and 3H in environmental toxicology and human carcinogenesis research. For 14C, AMS has a 1000-fold higher sensitivity than liquid scintillation decay counting, allowing the quantitation of attomole (10[-18] mole), or smaller, samples. Presently, the analysis of biological samples using AMS is limited by the requirement for highly specialized sample preparation procedures which are not compatible with standard chromatographs. The goal of Phase I is to develop techniques for the real-time coupling of a LC to the input of an AMS system, leading to the construction and testing of a LC-AMS interface in Phase II. This interface will be coupled to a compact biomedical AMS system developed by NSI in order to demonstrate, for the first time, the detection of labeled molecules from a LC using an AMS. It will also be suitable for use with other existing AMS systems. PROPOSED COMMERCIAL APPLICATIONS: The biomedical LC-AMS system will have widespread commercial applications in toxicology and new drug research. With this instrument, it will be possible to conduct drug metabolism and kinetics studies using three orders-of-magnitude less tracer activity than is possible today. The cost and size of the LC-AMS system will be compatible with installation at major medical research centers. The LC-AMS interface will also have a commercial market as a stand-alone instrument which will allow conversion of any existing AMS system to biomedical use.